TACL-2014-001: A Trial of Temsirolimus With Etoposide and Cyclophosphamide in Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkins Lymphoma
Patients must have one of the following:
- Acute Lymphoblastic Leukemia (ALL)
- Lymphoblastic Lymphoma
- Peripheral T-cell Lymphoma
This is a phase I study of temsirolimus (Torisel) combined with dexamethasone, cyclophosphamide and etoposide in patients with relapsed acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma (LL) or peripheral T-cell lymphoma (PTL). Studies have shown that mTOR inhibitors (MTI) inhibit growth of pre-B and T-cell ALL cell lines in vitro and in ALL xenograft models. The MTI temsirolimus was chosen for use in this study due to its weekly intravenous dosing, its more predictable blood levels, and availability of a single-agent pediatric MTD and its sustained biologic effect due to conversion to sirolimus. This study will determine the maximum tolerated dose of temsirolimus that can given in combination with dexamethasone, cyclophosphamide and etoposide in relapsed ALL, LL or PTL. A standard 3-patient cohort dose-escalation design will be used. Response to treatment will be evaluated. Biology tests will be done to evaluate minimal residual disease (MRD), temsirolimus' effect on glucocorticoid resistance, and mTOR inhibition.
- Ages eligible for study: 1 Year to 21 Years (Child, Adult)
- Bone marrow involvement defined as ALL ≥ 25% blasts (M2 or M3) with or without extramedullary involvement.
- Refractory bone marrow involvement defined as MRD ≥ 0.1% blasts done at a COG-approved MRD testing lab after most recent treatment regimen in the bone marrow (M23) and any CNS status. OR
- Newly diagnosed patients (T or B-cell ALL) with refractory bone marrow involvement after Consolidation therapy are eligible.
- First relapse B-cell ALL patients are eligible with refractory disease.
- Second or greater relapse B-cell patients are eligible at time of relapse or with refractory disease.
- First or greater relapse T-cell ALL patients are eligible at time of relapse or with refractory disease.
- Isolated CNS 2 or 3 patients with < 0.1% MRD bone marrow involvement are not eligible.
- Patient must have relapsed or refractory lymphoblastic lymphoma or peripheral T-cell lymphoma.
- Patient must have histologic verification of disease at original diagnosis.
- Patient must have evaluable or measurable disease documented by clinical or radiographic criteria or bone marrow disease present at study entry.
- Patients may have CNS 2 or 3 disease
- Karnofsky greater than or equal to 50% for patients > 16 years of age and Lansky greater than or equal to 50 for patients ≤ 16 years of age.
- Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy.
- Patients with leukemia or lymphoma who relapse while receiving maintenance chemotherapy will not be required to have a waiting period before enrollment onto this study.
- At least 14 days must have elapsed after the completion of cytotoxic therapy, with the exception of hydroxyurea.
- Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor.
- Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair
- Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines. or chimeric antigen receptor T cell (CART) therapy or tumor vaccines.
- Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of a monoclonal antibody. (ie: Rituximab = 66 days, Epratuzumab = 69 days). Patients must have been off blinatumomab infusion for at least 4 days and all drug-related toxicity must have resolved to grade 2 or lower as outlined in the inclusion and exclusion criteria
- XRT: At least 14 days after local palliative XRT (small port); At least 84 days must have elapsed if prior TBI, craniospinal XRT or if greater than or equal to 50% radiation of pelvis; At least 42 days must have elapsed if other substantial marrow radiation.
- Stem Cell Infusion: No evidence of active graft vs. host disease and at least 84 days must have elapsed after transplant or stem cell infusion.
- Adequate Bone Marrow Function.
- Adequate Renal Function.
- Adequate Liver Function.
- Adequate Cardiac Function.
- Adequate Pulmonary Function.
Detailed inclusion and exclusion criteria as listed on clinicaltrials.gov.
Eric S. Schafer, MD, MHS
Local Principal Investigator
Texas Children’s Cancer and Hematology Centers